1. Field of Invention
The present invention relates to a pyripyropene A biosynthetic gene.
2. Background Art
As disclosed in Japanese Patent Laid-Open Publication No. 360895/1992 (Patent Document 1) and Journal of Antibiotics (1993), 46 (7), 1168-9 (Non-patent Document 1), pyripyropene A has an inhibitory activity against ACAT (acyl CoA cholesterol acyltransferase). Application thereof to treatment of diseases caused by cholesterol accumulation or the like is expected.
Additionally, in Journal of Synthetic Organic Chemistry, Japan (1998), Vol. 56, No. 6, 478-488 (Non-patent Document 2), WO94/09147 (Patent Document 2), Japanese Patent Laid-Open Publication No. 184158/1994 (Patent Document 3), Japanese Patent Laid-Open Publication No. 239385/1996 (Patent Document 4), Japanese Patent Laid-Open Publication No. 259569/1996 (Patent Document 5), Japanese Patent Laid-Open Publication No. 269062/1996 (Patent Document 6), Japanese Patent Laid-Open Publication No. 269063/1996 (Patent Document 7), Japanese Patent Laid-Open Publication No. 269064/1996 (Patent Document 8), Japanese Patent Laid-Open Publication No. 269065/1996 (Patent Document 9), Japanese Patent Laid-Open Publication No. 269066/1996 (Patent Document 10), Japanese Patent Laid-Open Publication No. 291164/1996 (Patent Document 11) and Journal of Antibiotics (1997), 50 (3), 229-36 (Non-patent Document 3), pyripyropene analogs and derivatives, as well as ACAT inhibitory activities thereof have been disclosed.
Further, Applied and Environmental Microbiology (1995), 61 (12), 4429-35 (Non-patent Document 4) has disclosed that pyripyropene A has an insecticidal activity against Helicoverpa armigera larva. Still further, WO2004/060065 (Patent Document 12) has disclosed that pyripyropene A has insecticidal activities against Diamondback moth larva and Tenebrio molitor. 
In addition, WO2006/129714 (Patent Document 13) and WO2008/066153 (Patent Document 14) have disclosed that pyripyropene analogs have insecticidal activities against aphids.
Furthermore, as a pyripyropene A-producing bacterium, Aspergillus fumigatus FO-1289 strain is disclosed in Japanese Patent Laid-Open Publication No. 360895/1992 (Patent Document 1); Eupenicillium reticulosporum NRRL-3446 strain is in Applied and Environmental Microbiology (1995), 61 (12), 4429-35 (Non-patent Document 4); and Penicillium griseofulvum F1959 strain is in WO2004/060065 (Patent Document 12); and Penicillium coprobium PF1169 strain is in Journal of Technical Disclosure 500997/2008 (Patent Document 15).
Also, as a biosynthetic route of pyripyropene A, Journal of Organic Chemistry (1996), 61, 882-886 (Non-patent Document 5) and Chemical Review (2005), 105, 4559-4580 (Non-patent Document 6) have disclosed a putative biosynthetic route in Aspergillus fumigatus FO-1289 strain. These documents have disclosed that, in Aspergillus fumigatus FO-1289 strain, partial structures individually synthesized by polyketide synthase and prenyltransferase are linked to synthesize pyripyropene A by a cyclase.